title: Functionalized hydroxyethylamine based peptide nanostructures as potential inhibitors of falcipain-3, an essential proteases of Plasmodium falciparum.
abstract: Self-assembled peptide based nanostructures gained enough popularity due to their easy biocompatibility and numerous potential applications. An excellent model of self-assembly of hydroxyethylamine based peptide nanostructures was synthesized and characterized by DLS and TEM. Spherical nano structures of I and III were observed with particle size ∼50 and ∼80nm, respectively. Further, I and III were screened against anti-malarial target, falcipain-3 (FP3), a crucial cysteine protease involved as a major hemoglobinase of Plasmodium falciparum. Interestingly, compound III completely inhibited the activity of FP3. The effective concentration (1.5μM) of III found to be more potent than I. This biochemical result was substantiated by molecular-docking studies indicating III to be best inhibitor of FP3. This is the first report showing that bis hydroxethylamine based peptide nanostructures could be very effective inhibitor of malarial cysteine proteases.
authors.affiliation: Bio-organic Research Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India. brathi@svc.ac.in
authors.forename: Brijesh
authors.initials: B
authors.lastname: Rathi
authors.forename: Anil K
authors.initials: AK
authors.lastname: Singh
authors.forename: Ram
authors.initials: R
authors.lastname: Kishan
authors.forename: Neelu
authors.initials: N
authors.lastname: Singh
authors.forename: N
authors.initials: N
authors.lastname: Latha
authors.forename: S
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Kailash C
authors.initials: KC
authors.lastname: Pandey
authors.forename: Hemandra K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: Brajendra K
authors.initials: BK
authors.lastname: Singh
mesh_terms: D000588:Amines / Q000737:chemistry*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D062105:Molecular Docking Simulation; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000588:Amines; D000962:Antimalarials; D008024:Ligands; D010455:Peptides; D011480:Protease Inhibitors; D003546:Cysteine Endopeptidases; C443101:falcipain 3
keywords: Antimalarial chemotheraphy; BYZAHKRALXCGNO-XAZDILKDSA-N; Falcipain-3; Hemoglobin hydrolysis; Hydroxyethylamine; Molecular self-assembly; QRJCFENHSFVGNL-MSOLQXFVSA-N; WSDASMLFNPNZOK-JFYQQWHZSA-N